We used tree ring data (AD 1601–2007) to examine the occurrence of and climatic influences on spruce beetle (Dendroctonus rufipennis) outbreaks in south-central and southwest Alaska and found evidence of regional-scale outbreaks dating from the mid-1700s, related to climate variability at multiple temporal scales. Over interannual time scales (∼1–3 years), El Niño years, combined with severe late-summer drought, appeared to contribute significantly to spruce beetle outbreaks in the study area. Over multidecadal time scales (up to ∼40 years), cool-phase Pacific Decadal Oscillation (PDO) conditions tended to precede beetle outbreaks, regardless of the phase of El Niño-Southern Oscillation (ENSO). All sites showed low-severity disturbances attributed to spruce beetle damage, most notably during the 1810s. During other major periods of disturbance (i.e., 1870s, 1910s, 1970s), the effects of spruce beetle outbreaks were of moderate or higher severity. The highly synchronized timing of spruce beetle outbreaks at interannual to multidecadal scales, and particularly the association between cool-phase PDO conditions and beetle disturbance, suggests that climate (i.e., temperature, precipitation) is a primary driver of outbreaks in the study area. Our disturbance chronologies (mid-1700s to present) suggest that recent irruptions (1990s to present) in south-central and southwest Alaska are within the historical geographic range, but that outbreaks since the 1990s show greater spatiotemporal synchrony (i.e., more sites record high-severity infestations) than at any other time in the past ∼250 years.