Prothro moved to the professional ranks of the National Football League (NFL) in 1971 as head coach of the Los Angeles Rams, a position he held for two seasons.

In 1941, Prothro's versatility on the field helped him win the Jacobs award as the best blocker in the Southern Conference as the Blue Devils reached the 1942 Rose Bowl.

Prothro was selected in the fifth round of the 1942 NFL draft by the New York Giants,[1] but rejected the opportunity in favor of a budding coaching career and a brief attempt at professional baseball.

Over the next six years, Prothro used the single-wing formation as UCLA's backfield coach, helping the Bruins to an undefeated season and national championship in 1954.

This made USC fans infer that, if the Trojans had a strong showing against heavily favored Notre Dame, they might somehow get the Rose Bowl berth despite Oregon State's better record.

He was replaced by Dee Andros, the head coach at Idaho, whose Vandals had played Oregon State tough in 1964 in Corvallis, defeated 10–7 by a late third quarter OSU punt return.

[4] Integrated UCLA then faced all-white Tennessee in the newly built Liberty Bowl stadium in Memphis, Prothro's native city.

On the last play of the game, Tennessee defensive back Bob Petrella intercepted a UCLA pass to save a Volunteer win by a score of 37–34.

The Bruins, featuring a "dream backfield" of All-Americans Gary Beban and Mel Farr, lost only one game, at rainy Washington, 16–3, where Huskies' head coach Jim Owens had devoted his entire season to beating Prothro.

UCLA had beaten UW the season before, 28–24, with Prothro's trick play, the Z-streak in which a receiver trots towards the sideline like he's going out of the game and then runs a streak pattern unguarded by the inattentive defender.

It was speculated that the directors believed Beban could not play for UCLA in the Rose Bowl due to the broken ankle, thereby giving the Big Ten Conference representative, Purdue, a better chance to win.

Inflamed UCLA students who had gathered for the Rose Bowl celebration rally, took to the streets of Westwood in protest and actually blocked the 405 Freeway for a short time.

Ironically, Morgan was the force behind establishing a tie-breaking method adopted by the conference one year later in which only loss column counted; the first tiebreaker was head-to-head results, followed by overall record.

The Bruins, quarterbacked by a sensational junior college transfer Dennis Dummit who was discovered by Prothro, were undefeated until they faced #10 Stanford on the road.

Once again, Prothro was let down by now-senior kicker Zenon Andrusyshyn as he missed a short field goal late in the game with the score tied 20–20.

UCLA scored midway through the fourth quarter to take a 12–7 lead (knowing he need a win and not a tie to advance to the Rose Bowl, Prothro had the Bruins go for two after each touchdown and each attempt failed).

Secondly, on the winning touchdown pass reception, USC receiver Sam Dickerson appeared to be either out of bounds, out of the back of the end zone, or both.

UCLA also blew a 20-point fourth quarter lead against Oregon, when Ducks sophomore quarterback Dan Fouts rallied his team to three touchdowns and a 41–40 win.

Finally, there came the showdown with Stanford; the game was expected to be a shootout between UCLA quarterback Dennis Dummit and Heisman winner Jim Plunkett.

Prothro was frustrated by bizarre officiating at critical moments, numerous last minute narrow losses, and losing out of the Rose Bowl by the conference vote in 1966.

Dressed in a suit and tie, fedora, and thick black framed glasses, he looked more like he was going to a business meeting than to coach a football game.

Los Angeles Times sports columnist Jim Murray once suggested in jest that all the briefcase contained was "a couple of peanut-butter sandwiches."

However, Prothro left his mark on the team by trading many aging veterans, often to George Allen's Washington Redskins, and stocking up young talent and draft picks; players such as Lawrence McCutcheon, Isiah Robertson, Dave Elmendorf, Larry Brooks, Jim Bertelsen, Jack "Hacksaw" Reynolds, and Hall of Famer Jack Youngblood were the core of the Rams teams of the 1970s that won seven straight NFC Western division titles.

The San Diego Chargers hired Prothro as their new head coach on January 8, 1974, placing him in charge of rebuilding the once-proud franchise that had become mired in mediocrity and a drug scandal.

These drafts paid immediate dividends as the Chargers improved to 6–8 in 1976, and 7–7 in 1977, including a 12–7 win over rival Oakland that cost the Raiders the division title.

However, a 1–3 start, marked by a loss to the Raiders in what became known as the Holy Roller game of September 10, caused Prothro to abruptly resign as head coach, replaced by Don Coryell.

The Chargers finished 1978 with a 9–7 record, their first winning season since 1969, as the team Prothro helped build won three straight AFC Western Division titles and made the playoffs every year from 1979 to 1982.

Only an ill-advised interception in the end zone (when the Browns were in easy field goal range) in a 14–12 playoff loss to the Oakland Raiders cost Cleveland a shot at Prothro's former team, the Chargers, in the AFC title game.