Opposite words for insignificant:
momentous, overbearing, measurable, overriding, significant, prestigious, epochal, serious, worthwhile, consequential, profound, meaningful, decisive, illustrious, fundamental, probative, world-shaking, monumental, prodigious, preeminent, epoch-making, distinguished, principal, portentous, considerable, material, famous, great, all-important, evidential, pivotal, operative, overmastering, valuable, impressive, big, weighty, eminent, exceptional, chief, appreciable, key, major, large, worthy, dominant, important, notorious, noteworthy, noticeable, renowned, fatal, substantial, unfrivolous, conspicuous, prominent, discernible, probatory, earthshaking, remarkable, distinctive, essential, fateful, eventful, evidentiary, basic, striking, outstanding, world-shattering.
Usage samples:
  1. The officer paused a moment, glaring at him and Tom felt very unimportant and insignificant.
    "Tom Slade Motorcycle Dispatch Bearer", Percy Keese Fitzhugh.
  2. A certain intensity in his large grey eyes gave character to a face that was otherwise quite insignificant.
    "I Saw Three Ships and Other Winter Tales", Arthur Thomas Quiller-Couch.
  3. And he was only an insignificant clerk, with small prospect of ever being anything much better, for he had started the battle of life too late.
    "The Gloved Hand", Burton E. Stevenson.
  4. All they knew was that the President of an insignificant republic having ventured to " beard the English," he was to be punished accordingly, and brought to reason.
    "The Three Lieutenants", W.H.G. Kingston.