I had the same problem when I first started increasing from 20 mile rides to 50-60+ mile rides. My left knee would start hurting about ten miles in and get progressively worse until I was basically pedalling with only my right leg. It sucked.
A few things I did to fix the problem:
1. Adjusted my cleats. I realized that I had set up my cleats (SPD) to orient my foot straight forward. Seemed logical at the time, but that basically forced my foot into an unnatural position. I pronate quite a bit and my left foot really supinates, so I tried to center my shoe into my natural foot position. It helped a lot.
2. In order to adjust my left shoe toward the natural supination (cant) of my left foot, I bought some LeMond LeWedges and wedged my left cleat up. By doing that, I completely eliminated 100% of my knee pain. It was night and day. One ride, lots of pain. Next ride, zero pain.
3. I also take extra care to leave my left shoe fairly loose when I strap it on. I just force my foot up in the shoe before I fasten the straps, which essentially leaves my foot some extra room to move where it wants as I pedal, instead of locking it down to the pedal.
Before focusing on my foot position, I tried all kinds of saddle changes - forward, backward, up, down, tilted, you name it. None of that had any effect on my knee pain. Others have had luck with changing saddle position, but I didn't.
Anyway, I know that knee pain can be very, very frustrating, so I wish you luck and hope you find an easy solution!