Telica volcano, in north-west Nicaragua, is a young stratovolcano of intermediate magma composition producing frequent Vulcanian to phreatic explosive eruptions. The Telica stratigraphic record also includes examples of (pre)historic sub-Plinian activity. To refine our knowledge of this very active volcano, we analyzed major element composition and volatile content of melt inclusions from some stratigraphically significant Telica tephra deposits. These include: (1) the Scoria Telica Superior (STS) deposit (2000 to 200 years Before Present; Volcanic Explosive Index, VEI, of 2–3) and (2) pyroclasts from the post-1970s eruptive cycle (1982; 2011). Based on measurements with nanoscale secondary ion mass spectrometry, olivine-hosted (forsterite [Fo] > 80) glass inclusions fall into 2 distinct clusters: a group of H2O-rich (1.8–5.2 wt%) inclusions, similar to those of nearby Cerro Negro volcano, and a second group of CO2-rich (360–1700 μg/g CO2) inclusions (Nejapa, Granada). Model calculations show that CO2 dominates the equilibrium magmatic vapor phase in the majority of the primitive inclusions (XCO2 > 0.62–0.95). CO2, sulfur (generally < 2000 μg/g) and H2O are lost to the vapor phase during deep decompression (P > 400 MPa) and early crystallization of magmas. Chlorine exhibits a wide concentration range (400–2300 μg/g) in primitive olivine-entrapped melts (likely suggesting variable source heterogeneity) and is typically enriched in the most differentiated melts (1000–3000 μg/g). Primitive, volatile-rich olivine-hosted melt inclusions (entrapment pressures, 5–15 km depth) are exclusively found in the largest-scale Telica eruptions (exemplified by STS in our study). These eruptions are thus tentatively explained as due to injection of deep CO2-rich mafic magma into the shallow crustal plumbing system. More recent (post-1970), milder (VEI 1–2) eruptions, instead, do only exhibit evidence for low-pressure (P < 50–60 MPa), volatile-poor (H2O < 0.3–1.7 wt%; CO2 < 23–308 μg/g) magmatic conditions. These are manifested as andesitic magmas, recording multiple magma mixing events, in pyroxene inclusions. We propose that post-1970s eruptions are possibly related to the high viscosity of resident magma in shallow plumbing system (< 2.4 km), due to crystallization and degassing.