Linguistic knowledge, cognitive ability, and instruction influence how adults acquire a second orthography yet it remains unclear how different forms of instruction influence grain size sensitivity and subsequent decoding skill and speed. Thirty-seven monolingual, literate English-speaking adults were trained on a novel artificial orthography given initial instruction that directed attention to either large or small grain size units (i.e., words or letters). We examined how initial instruction influenced processing speed (i.e., reaction time (RT)) and sensitivity to different orthographic grain sizes (i.e., rimes and letters). Directing attention to large grain size units during initial instruction resulted in higher accuracy for rimes, whereas directing attention to smaller grain size units resulted in slower RTs across all measures. Additionally, phonological awareness skill modulated early learning effects, compensating for the limitations of the initial instruction provided. Collectively, these findings suggest that when adults are learning to read a second orthography, consideration should be given to how initial instruction directs attention to different grain sizes and to inherent phonological awareness ability.