Born in Troia, Foggia, Apulia, Italy, DePalma's family emigrated to the United States in 1883, when he was eight years old. As a young man of twenty-two, he began racing motorcycles before switching to cars, racing on dirt tracks between 1908 and 1911. In 1911, DePalma won the first Milwaukee Mile Championship Car race and was the AAA National Champion in 1912 and 1914.
In the 1912 Indianapolis 500, after leading for nearly 196 of the 200 laps, his Mercedes cracked a piston and only 2 laps remaining. he and his mechanic, Rupert Jeffkins, pushed the Gray Ghost across the finish line - and to disqualification - as Joe Dawson whizzed by to take the victory.
He went on to win the AAA National Championship that year, but was almost killed in an accident on October 5th at the Milwaukee Mile during the 400-mile Vanderbilt Cup. Chasing Caleb Bragg for the victory, DePalma crashed heavily on the last lap. Taken out of the ambulance bleeding profusely and suffering internal injuries, DePalma said, "Boys, don't forget that Caleb Bragg wasn't to blame. He gave me all the road." For such gallantry in defeat - and for his exciting victories - DePalma was vastly popular. Hospitalised for a considerable time, he recovered and was back to racing the following spring.
In 1914, he beat the great Barney Oldfield in the Vanderbilt Cup, run over the roads of Santa Monica, California, in what DePalma called his greatest race. Oldfield had been hired by the Mercer factory team to replace DePalma after DePalma had done all the development work on the car a year earlier. Clearly suprised by the move, DePalma vowed to beat Oldfield at every opportunity.
He got his first chance at the Vanderbilt Cup, racing a revived Mercedes Gray Ghost. DePalma suffered mechanical problems and only after the assistance of an associate who offered an engine bearing made of strong metal did he qualify for the race, some 40 seconds behind Oldfield.
Running a smooth, calculated race, DePalma moved through the field while Oldfield sped ahead. By the 13th lap, he was in fifth place.
On the 18th lap, DePalma assumed the lead when Oldfield pitted. When Oldfield returned, the battle was on and Oldfield took the lead on the 25th lap, just 10 from the finish. But there was one significant difference. Oldfield's pressing driving style had worn his tires. DePalma's were safe. However, DePalma slowed appreciably and signaled he was going to pit. Oldfield sped into the lead and then pitted the next time around, confident he had the race won.
However, as he sat in the pits, DePalma and the Gray Ghost sped by. DePalma had never pitted. With cold calculation and daring, he had won and beaten his rival.
He won at Elgin that year and followed that with his victory in the Indianapolis 500.
In June 1917 he lost to Barney Oldfield in a series of 10 to 25 mile match races ath the Milwaukee Mile. On February 12, 1919 at Daytona Beach, Florida, he drove a Packard to a world speed record of 149.875 mph over a measured mile. International competition began following the adoption of the three liter engine limit in the U.S. and Europe in 1920. DePalma began the year driving for the French manufacturer, Ballot. His Ballot vehicle was one of the fastest qualifiers at the 1920 Indy but bad luck dogged him in the race. However, DePalma traveled with other Americans to Le Mans to compete in the French Grand Prix. There, he finished second to the Duesenberg driven by fellow American, Jimmy Murphy.
Ralph DePalma had a small role in the 1920 Hollywood film, High Speed and in 1924 played the part of the Champion in an action/drama written by Wilfred Lucas titled Racing for Life. In 1923, he established the DePalma Manufacturing Company in Detroit to build race cars and engines for automobiles and aircraft.
Despite only one win at Indianapolis, DePalma dominated that annual classic time and time again only to be let down by mechanical problems just short of victory. He competed in 10 Indianapolis 500s, the last in 1925, a race won by his nephew Peter DePaolo. His record of leading 613 laps over a 10 year career stood until Al Unser broke it in 1987. As late as 1936 he was still setting records in stock cars.
Ralph DePalma retired from racing after a career in which he competed in 2,889 races, winning an astonishing 2,557. He died in South Pasadena, California in 1956 and was interred in the Holy Cross Cemetery in Culver City, California. The Mercedes in which he narrowly lost the 1912 Indianapolis 500 remains on display at the Indianapolis Motor Speedway Hall of Fame Museum.
DePalma was the brother of 500 competitor John DePalma and the uncle of 1925 Indy winner Pete DePaolo.