It is tempting to spend all your money on a 5-star Quarterback and a 5-star Wide Receiver. However, if your Offensive Line is weak, your QB will get sacked instantly, leading to injuries and fumbles. Invest in at least a 3-star Offensive Line to give yourself time to throw.
When scouting players, check their traits. Avoid players with the "Turnover Prone" trait, as they will fumble the ball frequently when tackled. Look for "Clutch" (plays better in the 4th quarter) or "Sprinter" (runs faster) instead.
Fumbles are devastating. If you are running with your QB or a Running Back and see a defender approaching, . This ends the play immediately and protects the ball.