That has always been an issue since the first Android phone came out back a couple of years ago.
Most new Android phones (Thunderbolt included), use a hardware proximity sensor to actually turn off the screen when you hold it up to your face to prevent accidental pushing of the keys.
You can see how this works by dialing a number (say like your voicemail to test), then if you block the light closely near the speaker at the top of the phone, you will see the screen turn off, move you hand away and it will turn back on.
It may be that the way you are holding the phone while talking may not always be activating the proximity sensor, so you are able to "touch" the mute button with your face on occasion.
i used to do that all the time as well. The only way I found to prevent it would be to actually lock the screen while on a call. It's a hassle, but it will prevent you from pushing anything with your face while calling. I do find myself using speakerphone alot as well or using a headset.
Hope that helps.