diff --git a/Formula/wxpython.rb b/Formula/wxpython.rb
index 331b5db171ce..4fbaa2d75e31 100644
--- a/Formula/wxpython.rb
+++ b/Formula/wxpython.rb
@@ -3,10 +3,9 @@ class Wxpython < Formula
 
   desc "Python bindings for wxWidgets"
   homepage "https://www.wxpython.org/"
-  url "https://files.pythonhosted.org/packages/b0/4d/80d65c37ee60a479d338d27a2895fb15bbba27a3e6bb5b6d72bb28246e99/wxPython-4.1.1.tar.gz"
-  sha256 "00e5e3180ac7f2852f342ad341d57c44e7e4326de0b550b9a5c4a8361b6c3528"
+  url "https://files.pythonhosted.org/packages/d9/33/b616c7ed4742be6e0d111ca375b41379607dc7cc7ac7ff6aead7a5a0bf53/wxPython-4.2.0.tar.gz"
+  sha256 "663cebc4509d7e5d113518865fe274f77f95434c5d57bc386ed58d65ceed86c7"
   license "LGPL-2.0-or-later" => { with: "WxWindows-exception-3.1" }
-  revision 3
 
   bottle do
     sha256 cellar: :any, arm64_monterey: "7b558516617be5aa563cf1250276eea3eda660e19bdf8bf66417aa55215992ea"
@@ -16,51 +15,45 @@ class Wxpython < Formula
     sha256 cellar: :any, catalina:       "363cff6b220e1d12e1075e3dfbb580eab83c0fea65f3c4f398d2d6eba80c5145"
   end
 
-  depends_on "freetype"
-  depends_on "jpeg-turbo"
-  depends_on "libpng"
-  depends_on "libtiff"
+  depends_on "doxygen" => :build
+  depends_on "sip" => :build
   depends_on "numpy"
   depends_on "pillow"
-  # The current stable release 4.1.1 is incompatible with Python 3.10.
-  # Requires backporting multiple upstream commits (e.g. PR 2026, 2039, 2062, ...)
-  # TODO: Update to `python@3.10` on next release.
-  # Ref: https://src.fedoraproject.org/rpms/python-wxpython4/commits/
-  depends_on "python@3.9"
+  depends_on "python@3.10"
   depends_on "six"
-  depends_on "tcl-tk"
-
-  uses_from_macos "zlib"
+  depends_on "wxwidgets"
 
   on_linux do
     depends_on "pkg-config" => :build
     depends_on "gtk+3"
   end
 
-  def install
-    # Work around error: [Errno 2] No such file or directory: 'brew'
-    # Try removing in the next release.
-    ENV["SETUPTOOLS_USE_DISTUTILS"] = "stdlib"
-
-    # Fix build of included wxwidgets:
-    # https://github.com/wxWidgets/Phoenix/issues/1247
-    # https://github.com/Homebrew/homebrew-core/pull/58988
-    inreplace "buildtools/build_wxwidgets.py" do |s|
-      s.gsub! "#wxpy_configure_opts.append(\"--enable-monolithic\")",
-              "wxpy_configure_opts.append(\"--disable-precomp-headers\")"
-    end
-
-    inreplace "wscript", "MACOSX_DEPLOYMENT_TARGET = \"10.6\"",
-                         "MACOSX_DEPLOYMENT_TARGET = \"#{MacOS.version}\""
+  # Fix build scripts depending on attrdict3 even though only used on Windows.
+  # Remove once upstream PR is merged and in release.
+  # PR ref: https://github.com/wxWidgets/Phoenix/pull/2224
+  patch do
+    url "https://github.com/wxWidgets/Phoenix/commit/2e9169effa9abf14f34f8436a791b8829eea7774.patch?full_index=1"
+    sha256 "932b3decf8fe5bd982c857796f0b9d936c6a080616733b98ffbd2d3229692e20"
+  end
 
-    if OS.mac? && (sdk = MacOS.sdk_path_if_needed)
-      ENV.append_to_cflags "-I#{sdk}/usr/include"
-    end
-    system "python3.9", *Language::Python.setup_install_args(prefix)
+  def install
+    ENV["DOXYGEN"] = Formula["doxygen"].opt_bin/"doxygen"
+    python = "python3.10"
+    system python, "-u", "build.py", "dox", "touch", "etg", "sip", "build_py",
+                   "--release",
+                   "--use_syswx",
+                   "--prefix=#{prefix}",
+                   "--jobs=#{ENV.make_jobs}",
+                   "--verbose",
+                   "--nodoc"
+    system python, *Language::Python.setup_install_args(prefix, python),
+                   "--skip-build",
+                   "--install-platlib=#{prefix/Language::Python.site_packages(python)}"
   end
 
   test do
-    output = shell_output("python3.9 -c 'import wx ; print(wx.__version__)'")
+    python = Formula["python@3.10"].opt_bin/"python3.10"
+    output = shell_output("#{python} -c 'import wx ; print(wx.__version__)'")
     assert_match version.to_s, output
   end
 end