diff --git a/easybuild/framework/easyblock.py b/easybuild/framework/easyblock.py
index 87e5660e2b..a786cbea2b 100644
--- a/easybuild/framework/easyblock.py
+++ b/easybuild/framework/easyblock.py
@@ -1401,12 +1401,24 @@ def make_module_pythonpath(self):
             candidate_paths = (os.path.relpath(path, self.installdir) for path in glob.glob(python_subdir_pattern))
             python_paths = [path for path in candidate_paths if re.match(r'lib/python\d+\.\d+/site-packages', path)]
 
+            # determine whether Python is a runtime dependency;
+            # if so, we assume it was installed with EasyBuild, and hence is aware of $EBPYTHONPREFIXES
             runtime_deps = [dep['name'] for dep in self.cfg.dependencies(runtime_only=True)]
-            use_ebpythonprefixes = all([
-                'Python' in runtime_deps,
-                build_option('prefer_python_search_path') == EBPYTHONPREFIXES,
-                not self.cfg['force_pythonpath']
-            ])
+
+            # don't use $EBPYTHONPREFIXES unless we can and it's preferred or necesary (due to use of multi_deps)
+            use_ebpythonprefixes = False
+            multi_deps = self.cfg['multi_deps']
+
+            if 'Python' in runtime_deps:
+                self.log.info("Found Python runtime dependency, so considering $EBPYTHONPREFIXES...")
+
+                if build_option('prefer_python_search_path') == EBPYTHONPREFIXES:
+                    self.log.info("Preferred Python search path is $EBPYTHONPREFIXES, so using that")
+                    use_ebpythonprefixes = True
+
+            elif multi_deps and 'Python' in multi_deps:
+                self.log.info("Python is listed in 'multi_deps', so using $EBPYTHONPREFIXES instead of $PYTHONPATH")
+                use_ebpythonprefixes = True
 
             if python_paths:
                 # add paths unless they were already added
diff --git a/easybuild/framework/easyconfig/default.py b/easybuild/framework/easyconfig/default.py
index db1e12c324..438bcea4e1 100644
--- a/easybuild/framework/easyconfig/default.py
+++ b/easybuild/framework/easyconfig/default.py
@@ -115,7 +115,6 @@
     'patches': [[], "List of patches to apply", BUILD],
     'prebuildopts': ['', 'Extra options pre-passed to build command.', BUILD],
     'preconfigopts': ['', 'Extra options pre-passed to configure.', BUILD],
-    'force_pythonpath': [False, "Force use of PYTHONPATH for python seearch path when possible.", BUILD],
     'preinstallopts': ['', 'Extra prefix options for installation.', BUILD],
     'pretestopts': ['', 'Extra prefix options for test.', BUILD],
     'postinstallcmds': [[], 'Commands to run after the install step.', BUILD],
diff --git a/test/framework/toy_build.py b/test/framework/toy_build.py
index 76ef640b29..edd9e94fcc 100644
--- a/test/framework/toy_build.py
+++ b/test/framework/toy_build.py
@@ -4242,15 +4242,16 @@ def test_toy_python(self):
         """
         Test whether $PYTHONPATH or $EBPYTHONPREFIXES are set correctly.
         """
-        # generate fake Python module that we can use as runtime dependency for toy
+        # generate fake Python modules that we can use as runtime dependency for toy
         # (required condition for use of $EBPYTHONPREFIXES)
         fake_mods_path = os.path.join(self.test_prefix, 'modules')
-        fake_python_mod = os.path.join(fake_mods_path, 'Python', '3.6')
-        if get_module_syntax() == 'Lua':
-            fake_python_mod += '.lua'
-            write_file(fake_python_mod, '')
-        else:
-            write_file(fake_python_mod, '#%Module')
+        for pyver in ('2.7', '3.6'):
+            fake_python_mod = os.path.join(fake_mods_path, 'Python', pyver)
+            if get_module_syntax() == 'Lua':
+                fake_python_mod += '.lua'
+                write_file(fake_python_mod, '')
+            else:
+                write_file(fake_python_mod, '#%Module')
         self.modtool.use(fake_mods_path)
 
         test_ecs = os.path.join(os.path.dirname(__file__), 'easyconfigs', 'test_ecs')
@@ -4284,8 +4285,8 @@ def test_toy_python(self):
         self.assertTrue(pythonpath_regex.search(toy_mod_txt),
                         f"Pattern '{pythonpath_regex.pattern}' found in: {toy_mod_txt}")
 
-        test_ec_txt += "\ndependencies = [('Python', '3.6', '', SYSTEM)]"
-        write_file(test_ec, test_ec_txt)
+        # if Python is listed as runtime dependency, then $EBPYTHONPREFIXES is used if it's preferred
+        write_file(test_ec, test_ec_txt + "\ndependencies = [('Python', '3.6', '', SYSTEM)]")
         self.run_test_toy_build_with_output(ec_file=test_ec, extra_args=args)
         toy_mod_txt = read_file(toy_mod)
 
@@ -4293,13 +4294,13 @@ def test_toy_python(self):
         self.assertTrue(ebpythonprefixes_regex.search(toy_mod_txt),
                         f"Pattern '{ebpythonprefixes_regex.pattern}' found in: {toy_mod_txt}")
 
-        test_ec_txt += "\nforce_pythonpath = True"
-        write_file(test_ec, test_ec_txt)
+        # if Python is listed in multi_deps, then $EBPYTHONPREFIXES is used, even if it's not explicitely preferred
+        write_file(test_ec, test_ec_txt + "\nmulti_deps = {'Python': ['2.7', '3.6']}")
         self.run_test_toy_build_with_output(ec_file=test_ec)
         toy_mod_txt = read_file(toy_mod)
 
-        self.assertTrue(pythonpath_regex.search(toy_mod_txt),
-                        f"Pattern '{pythonpath_regex.pattern}' found in: {toy_mod_txt}")
+        self.assertTrue(ebpythonprefixes_regex.search(toy_mod_txt),
+                        f"Pattern '{ebpythonprefixes_regex.pattern}' found in: {toy_mod_txt}")
 
 
 def suite():