Short version

1. Download
2. Extract
3. Double-click DisableDefender.reg

Explanation

By far the most effective and clean way to permanently disable Windows Defender in Windows 10 is via Group Policy, as described by Aaron Hoffman. Unfortunately, Windows 10 Home lacks the necessary tools.

Here's a registry file that contains the changes made by gpedit.msc on a Windows 10 Pro machine. It's been tested on Windows 10 Home as well. Save the file as DisableDefender.reg with Windows-style line endings and double-click it to import it into your registry.

Windows Registry Editor Version 5.00

[HKEY_LOCAL_MACHINE\SOFTWARE\Policies\Microsoft\Windows Defender]
"DisableAntiSpyware"=dword:00000001
"DisableRoutinelyTakingAction"=dword:00000001

If you ever want to re-enable Defender, change 00000001 to 00000000 on both lines.

You can download the files to disable and re-enable defender from Gist.

Note: This may not work any more as of feature update 1909.

Short version

1. Download
2. Extract
3. Double-click DisableDefender.reg

Explanation

By far the most effective and clean way to permanently disable Windows Defender in Windows 10 is via Group Policy, as described by Aaron Hoffman. Unfortunately, Windows 10 Home lacks the necessary tools.

Here's a registry file that contains the changes made by gpedit.msc on a Windows 10 Pro machine. It's been tested on Windows 10 Home as well. Save the file as DisableDefender.reg with Windows-style line endings and double-click it to import it into your registry.

Windows Registry Editor Version 5.00

[HKEY_LOCAL_MACHINE\SOFTWARE\Policies\Microsoft\Windows Defender]
"DisableAntiSpyware"=dword:00000001
"DisableRoutinelyTakingAction"=dword:00000001

If you ever want to re-enable Defender, change 00000001 to 00000000 on both lines.

You can download the files to disable and re-enable defender from Gist.