The phenylpropanoid and flavonoid pathways are well known for their function towards plant development and defense. Oil palm seedlings from a single cross challenged with Ganoderma boninense displayed different severity of infection after six and fourteen months post inoculation (mpi). Transcripts from phenylpropanoid and flavonoid pathways, and transcription factors related to secondary cell wall formation were compared based on external and internal symptom classification. This long term infection study revealed that the oil palm roots responded to G. boninense and regulated both phenylpropanoid and flavonoid pathways during infection. The expression of PAL2 and PAL3 were significantly higher at 6 mpi in symptomatic compared to asymptomatic and control seedlings. However, the expression of all PAL genes were down-regulated at 14 mpi for both symptomatic and asymptomatic seedlings. In the monolignol and lignin pathways, down-regulation of COMT in symptomatic and CCR in asymptomatic seedlings was observed at 14 mpi but not at 6 mpi suggesting a possible change in lignin composition likely related to observed resistance. The expression of transcription factors for secondary cell wall and monolignol (MYB58, MYB63 and SND1) biosynthesis showed down-regulation in symptomatic seedlings, also suggesting a link between cell wall biosynthesis and disease resistance. Genes that regulate the flavonoid pathway were mostly down-regulated in both symptomatic seedlings at both 6 mpi and 14 mpi indicating a possibility of pathway suppression after challenge with G. boninense. Prolonged G. boninense exposure suggested that oil palm seedlings responded differently in terms of phenylpropanoid and flavonoid pathway expression in conferring defense and disease resistance.