Anderson joined fellow Sooner quarterback Claude Arnold in Edmonton for the 1952 season. Anderson played from 1952 to 1957 with the Edmonton Eskimos, during which time, he earned the nickname "Blood & Guts" for his tough on field performance. During his time with the Eskimos, Frank was a 5-time defensive All-star. Also during his tenure, the Eskimos played in the 1952 Grey Cup, losing to the Toronto Argonauts. From 1954 through 1956, the Eskimos won three Grey Cups in a row; all were played against the Montreal Alouettes led by legendary quarterback Sam 'The Rifle' Etcheverry. Anderson was inducted (posthumously) onto the Commonwealth Stadium Wall of Honour in October 1985, the 8th former player honored.