Purchase destination tickets as far in advance as possible for the best prices and the best reserved seats (when available).
Check domestic fares at Amtrak.com. Ask about excursion fares, which, if available, can save you nearly half the round-trip fare. Also inquire about special rates for seniors, youths and families.
Catch the train from its point of origin (even if another stop is closer). It's often the only way to snag seats for the long haul, especially if you have a group traveling together.
Get sleeper reservations for an overnight trip with four or fewer people; the comfort is worth the cost if you can afford it. Otherwise, choose either a six-sleeper or general seating to save you a lot of money (although you may also lose a bit of sleep).