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The street begins at the intersection of Forum Drive and Strawberry Avenue in Strawberry and runs south-east through the incorporated city of Davis until it ends at a T-junction with Little Bighorn Avenue in Rancho, Los Santos. It has connections to Davis Avenue, Brouge Avenue, Roy Lowenstein Boulevard and Jamestown Street.
Macdonald Street runs parallel to the larger Carson Avenue and holds little of interest; it passes the Davis Courts Building and a fire station but is otherwise mostly tenements, single-family homes and small businesses.