diff --git a/gnu/packages/bioinformatics.scm b/gnu/packages/bioinformatics.scm
index 481a2a3bcb..9872933693 100644
--- a/gnu/packages/bioinformatics.scm
+++ b/gnu/packages/bioinformatics.scm
@@ -3563,11 +3563,6 @@ (define-public pbtranscript-tofu
       (build-system python-build-system)
       (arguments
        `(#:python ,python-2
-         ;; With standard flags, the install phase attempts to create a zip'd
-         ;; egg file, and fails with an error: 'ZIP does not support timestamps
-         ;; before 1980'
-         #:configure-flags '("--single-version-externally-managed"
-                             "--record=pbtranscript-tofu.txt")
          #:phases
          (modify-phases %standard-phases
            (add-after 'unpack 'enter-directory
@@ -7576,19 +7571,7 @@ (define-public pepr
     (build-system python-build-system)
     (arguments
      `(#:python ,python-2 ; python2 only
-       #:tests? #f ; no tests included
-       #:phases
-       (modify-phases %standard-phases
-         ;; When setuptools is used a ".egg" archive is generated and
-         ;; installed.  This makes it hard to actually run PePr.  This issue
-         ;; has been reported upstream:
-         ;; https://github.com/shawnzhangyx/PePr/issues/9
-         (add-after 'unpack 'disable-egg-generation
-           (lambda _
-             (substitute* "setup.py"
-               (("from setuptools import setup")
-                "from distutils.core import setup"))
-             #t)))))
+       #:tests? #f)) ; no tests included
     (propagated-inputs
      `(("python2-numpy" ,python2-numpy)
        ("python2-scipy" ,python2-scipy)
diff --git a/gnu/packages/pdf.scm b/gnu/packages/pdf.scm
index e447ef1603..b86f5efbfa 100644
--- a/gnu/packages/pdf.scm
+++ b/gnu/packages/pdf.scm
@@ -638,11 +638,6 @@ (define-public python-reportlab
                (base32
                 "0rz2pg04wnzjjm2f5a8ik9v8s54mv4xrjhv5liqjijqv6awh12gl"))))
     (build-system python-build-system)
-    (arguments
-     ;; Prevent creation of the egg. Without this flag, various artifacts
-     ;; from the build inputs end up in the final python3 output. It also
-     ;; works around https://debbugs.gnu.org/cgi/bugreport.cgi?bug=20765 .
-     `(#:configure-flags '("--single-version-externally-managed" "--root=/")))
     (propagated-inputs
      `(("python-pillow" ,python-pillow)))
     (home-page "http://www.reportlab.com")
diff --git a/gnu/packages/python.scm b/gnu/packages/python.scm
index f103706533..3fcd92dc83 100644
--- a/gnu/packages/python.scm
+++ b/gnu/packages/python.scm
@@ -2800,12 +2800,6 @@ (define-public python-sphinx-rtd-theme
         (base32
          "19nw3rn7awplcdrz63kg1njqwkbymfg9lwn7l2grhdyhyr2gaa8g"))))
     (build-system python-build-system)
-    (arguments
-     `(;; With standard flags, the install phase attempts to create a zip'd
-       ;; egg file, and fails with an error: 'ZIP does not support timestamps
-       ;; before 1980'
-       #:configure-flags '("--single-version-externally-managed"
-                           "--record=sphinx-rtd-theme.txt")))
     (inputs
      `(("python-docutils" ,python-docutils)
        ("python-sphinx" ,python-sphinx)))
@@ -3988,12 +3982,7 @@ (define-public python2-elib.intl
     (arguments
      ;; incompatible with Python 3 (exception syntax)
      `(#:python ,python-2
-       #:tests? #f
-       ;; With standard flags, the install phase attempts to create a zip'd
-       ;; egg file, and fails with an error: 'ZIP does not support timestamps
-       ;; before 1980'
-       #:configure-flags '("--single-version-externally-managed"
-                           "--record=elib.txt")))
+       #:tests? #f))
     (home-page "https://github.com/dieterv/elib.intl")
     (synopsis "Enhanced internationalization for Python")
     (description
@@ -4026,17 +4015,6 @@ (define-public python-pillow
     ;; Note: setuptools used at runtime for pkg_resources
     (arguments
      `(#:phases (modify-phases %standard-phases
-                  (add-before
-                   'install 'disable-egg-compression
-                   (lambda _
-                     ;; Leave the .egg uncompressed since compressing it would
-                     ;; prevent the GC from identifying run-time dependencies.
-                     ;; See <http://bugs.gnu.org/20765>.
-                     (let ((port (open-file "setup.cfg" "a")))
-                       (display "\n[easy_install]\nzip_ok = 0\n"
-                                port)
-                       (close-port port)
-                       #t)))
                   (add-after
                    'install 'check-installed
                    (lambda _
@@ -6520,15 +6498,7 @@ (define-public python-libarchive-c
                        (substitute* "libarchive/ffi.py"
                          (("find_library\\('archive'\\)")
                           (string-append "'" libarchive
-                                         "/lib/libarchive.so'"))))
-
-                     ;; Do not make a compressed egg (see
-                     ;; <http://bugs.gnu.org/20765>).
-                     (let ((port (open-file "setup.cfg" "a")))
-                       (display "\n[easy_install]\nzip_ok = 0\n"
-                                port)
-                       (close-port port)
-                       #t))))))
+                                         "/lib/libarchive.so'")))))))))
     (inputs
      `(("libarchive" ,libarchive)))
     (home-page "https://github.com/Changaco/python-libarchive-c")
@@ -9454,9 +9424,6 @@ (define-public python-pkgconfig
       `(;; Tests fail with "ValueError: _type_ 'v' not supported" on Python 3,
         ;; and on Python 2 they need the dl module deprecated since Python 2.6.
         #:tests? #f
-        ;; Prevent creation of the egg. This works around
-        ;; https://debbugs.gnu.org/cgi/bugreport.cgi?bug=20765 .
-        #:configure-flags '("--single-version-externally-managed" "--root=/")
         ;; Hard-code the path to pkg-config.
         #:phases
         (modify-phases %standard-phases
@@ -10979,10 +10946,7 @@ (define-public python-pytest-pep8
                 "06032agzhw1i9d9qlhfblnl3dw5hcyxhagn7b120zhrszbjzfbh3"))))
     (build-system python-build-system)
     (arguments
-     `(#:tests? #f ; Fails with recent pytest and pep8. See upstream issues #8 and #12.
-       ;; Prevent creation of the egg. This works around
-       ;; https://debbugs.gnu.org/cgi/bugreport.cgi?bug=20765 .
-       #:configure-flags '("--single-version-externally-managed" "--root=/")))
+     `(#:tests? #f)) ; Fails with recent pytest and pep8. See upstream issues #8 and #12.
     (native-inputs
      `(("python-pytest" ,python-pytest)))
     (propagated-inputs
@@ -11007,10 +10971,7 @@ (define-public python-pytest-flakes
                 "0flag3n33kbhyjrhzmq990rvg4yb8hhhl0i48q9hw0ll89jp28lw"))))
     (build-system python-build-system)
     (arguments
-     `(;; Prevent creation of the egg. This works around
-       ;; https://debbugs.gnu.org/cgi/bugreport.cgi?bug=20765 .
-       #:configure-flags '("--single-version-externally-managed" "--root=/")
-       #:phases
+     `(#:phases
        (modify-phases %standard-phases
          (delete 'check)
          (add-after 'install 'check
diff --git a/gnu/packages/statistics.scm b/gnu/packages/statistics.scm
index 950c3ec64f..cca08d26a8 100644
--- a/gnu/packages/statistics.scm
+++ b/gnu/packages/statistics.scm
@@ -1394,13 +1394,7 @@ (define-public python-patsy
     (arguments
      `(#:phases
        (modify-phases %standard-phases
-         (replace 'check (lambda _ (zero? (system* "nosetests" "-v"))))
-         (add-after 'unpack 'prevent-generation-of-egg-archive
-          (lambda _
-            (substitute* "setup.py"
-              (("from setuptools import setup")
-               "from distutils.core import setup"))
-            #t)))))
+         (replace 'check (lambda _ (zero? (system* "nosetests" "-v")))))))
     (propagated-inputs
      `(("python-numpy" ,python-numpy)
        ("python-scipy" ,python-scipy)
diff --git a/gnu/packages/tls.scm b/gnu/packages/tls.scm
index 608fd6a080..607fa33b27 100644
--- a/gnu/packages/tls.scm
+++ b/gnu/packages/tls.scm
@@ -437,15 +437,6 @@ (define-public python-acme
     (arguments
      `(#:phases
        (modify-phases %standard-phases
-         (add-before 'install 'disable-egg-compression
-           (lambda _
-             ;; Do not compress the egg.
-             ;; See <http://bugs.gnu.org/20765>.
-             (let ((port (open-file "setup.cfg" "a")))
-               (display "\n[easy_install]\nzip_ok = 0\n"
-                        port)
-               (close-port port)
-               #t)))
          (add-after 'install 'docs
            (lambda* (#:key outputs #:allow-other-keys)
              (let* ((out (assoc-ref outputs "out"))
diff --git a/gnu/packages/tor.scm b/gnu/packages/tor.scm
index e6fbf6e005..fe079fb104 100644
--- a/gnu/packages/tor.scm
+++ b/gnu/packages/tor.scm
@@ -208,11 +208,7 @@ (define-public onionshare
            ;; After all the patching we run the tests after installing.
            ;; This is also a known issue:
            ;; https://github.com/micahflee/onionshare/issues/284
-           (lambda _ (zero? (system* "nosetests" "test")))))
-       ;; can't compress the egg because it expects to find all the resources
-       ;; inside the egg as though it were a folder.
-       #:configure-flags '("--single-version-externally-managed" "--root=/")
-       ))
+           (lambda _ (zero? (system* "nosetests" "test")))))))
     (native-inputs
      `(("python-nose" ,python-nose)))
     (inputs